This project is designed to investigate the effects of ethyl alcohol on the electrical and synaptic behavior of neurons in the nervous system of the gastrointestinal tract. The results of the studies are expected to provide basic neurophysiological information that will improve insight into: (1) the gastrointestinal disturbances associated with ethanol ingestion; (2) the mechanisms of action of ethanol on individual nerve cells; (3) ways in which alcohol disrupts synaptic function within integrative circuitry of the nervous system. Intracellular electrical recording methods will be used to evaluate the functional behavior of neurons in the myenteric plexus of the guinea-pig small intestine, in vitro. This will be done both by acute exposure of the neurons to ethanol by application in the tissue bath and by recording from neurons in the small intestine of guinea-pigs that have developed tolerance to chronic administration of ethanol over a period of several days. Some of the specialized functions on which ethanol will be investigated are: (1) Hyperpolarizing after-potentials that reflect operation of calcium-dependent potassium channels in the neuronal membranes; (2) Closure of calcium-dependent potassium channels and the dramatic enhancement of neuronal excitability that occurs during slow synaptic excitation; (3) Interaction of cholinergic, peptidergic and aminergic neurotransmitters with postsynaptic receptors; (4) Presynaptic receptors and the presynaptic mechanisms of neurotransmitter release at enteric neuronal synapses; (5) Receptor operation of adenylate cyclase and second messenger function of cAMP in slow synaptic excitation.